Interleukin-17 (IL-17A) is an inflammatory cytokine initially identified as a transcript selectively expressed by activated T cells. IL-17A and IL-17F bind and activate IL-17RA. IL-17RA has been shown to be important in regulating immune responses. Activation of the IL-17RA leads to production of cytokines, chemokines, growth factors, and other proteins that contribute to the symptoms and/or pathology of numerous diseases. IL-17A is an inflammatory cytokine that induces the production of cytokines and other mediators leading to diseases and physiological effects such as inflammation, cartilage degradation, and bone resorption. IL-17A may play a role in a number of inflammatory conditions including arthritis (rheumatoid arthritis), psoriasis, inflammatory bowel disease, multiple sclerosis, and asthma. (Li et al., 2004, Huazhong Univ. Sci. Technolog. Med. Sci. 24:294-296; Fujino et al., 2003, Gut. 52:65-70; Kauffman et al., 2004, J. Invest. Dermatol. 123:1037-1044; Mannon et al., 2004, N. Engl. J Med. 351:2069-2079; Matusevicius et al., 1999, Mult Scler 5, 101-104; Linden et al., Eur Respir J. 2000 May; 15(5):973-7; Molet et al., 2001, J. Allergy Clin. Immunol. 108:430-438). Recent studies have suggested that IL-17F plays a role in the induction of inflammatory responses (Oda et al., 2006, American J. Resp. Crit. Care Medicine, Jan. 15, 2006; Numasaki et al., 2004, Immunol Lett. 95:97-104).
IL-17 Receptor A (IL-17RA) has been shown to bind and be activated by IL-17A and IL-17F. Five additional IL-17-like ligands (IL-17B-IL-17F) and four additional IL-17RA-like receptors (IL-17RB-IL-17RE) have been identified (Kolls and Linden, 2004, Immunity 21:467-476; Gaffen, 2009, Nat Rev Immunol 8:556-568). IL-17 Receptor C (IL-17RC) has been shown to bind and be activated by IL-17A and IL-17F. IL-17RA and IL-17RC form a functional heteromeric receptor complex (Toy et al., 2006, J. Immunol. 177:36-39; McAllister et al., 2005, J. Immunol. 175:404-412). In addition, IL-17 Receptor B (IL-17RB) has also been shown to require IL-17RA for IL-25 mediated activity (Rickel, et al., 2008, J. Immunol. 181:4299-4310), and IL-17RD interacts with IL-1-17RA to mediate IL-17 signaling (Rong, et al., 2009, Cell Research 19:208-215).